The long term goals of our research are to understand the biochemical processes by which androgens and related hormones affect the prostate, seminal vesicles, and other target organs and also to provide molecular bases for treatment of abnormal growth of hormone sensitive and insensitive organs, such as benign prostate hyperplasia (BPH) and prostatic cancers. The specific aims for the next 5 year period are: (1). To study the structure and functions of human and rat receptors for 5-androstene-3beta, 17beta-diol (5A-diol). This study includes characterization of receptors for 5A-diol, cloning of their cDNAs, and production of poly- and monoclonal antibodies to the receptors. (2). To study orphan receptors whose cDNAs we have isolated in the past or will be found during the isolation of cDNAs for the 5A-diol receptors. Poly- and monoclonal antibodies to the orphan receptors will be produced. We will also screen potential ligands (new hormones?) for orphan receptors. (3). To analyze mutation in androgen receptor (AR) genes in androgen- sensitive and insensitive prostate cancer cells and to identif AR sequences/domain structures and cellular factors that are important in the modulation of the transcriptional activity and intracellular recycling/replenishment of AR in prostate cells. Androgens including 5A-diol has unique effects in many male and female target organs and can also regulate the growth of androgen or estrogen sensitive tumors. The study of the structures and mutations of ARs is essential in understanding the abnormality in androgen actions. Since the functions of ARs may be modulated by cellular protein factors, identification and characterization of these factors may be important in understanding wholly how gene expression is positively or negatively modulated by androgens. 5A-diol may act by binding to a new receptor. Antagonists of 5A-diol binding to the receptor may have therapeutic values in traeating cancer and other disorders associated with 5A-diol.